These results are consistent with the hypothesis that the enrichments for DNMT3A mutations in bone metastases, NOTCH1 mutations in skin metastases, and ASXL1 amplifications/PTEN deletions in brain metastases are biologically relevant, either as adaptations that arise in response to the local tumor microenvironment or as drivers of site-specific patterns of metastasis. This evidence concerns the gene NOTCH1 and neoplasm.